Refining the Effects Observed in a Developmental Neurobehavioral Study of Ammonium Perchlorate Administered Orally in Drinking Water to Rats. II. Behavioral and Neurodevelopment Effects

Abstract

A developmental neurotoxicity study was conducted to generate additional data on the potential functional and morphological hazard to the central nervous system caused by ammonium perchlorate in offspring from in utero and lactation exposure. Female Sprague-Dawley rats (23 to 25/group) were given continuous access to 0 (carrier), 0.1, 1.0, 3.0, and 10.0 mg/kg-day perchlorate in the drinking water beginning 2 weeks prior to mating and continuing through day 10 of lactation for the behavioral function assessment or given continuous access to 0 (carrier), 0.1, 1.0, 3.0, and 30.0 mg/kg-day beginning on gestation day 0 and continuing through day 10 of lactation for neurodevelopment assessments. Motor activity was conducted on postpartum days 14, 18, and 22 and juvenile brain weights, neurohistopathological examinations, and regional brain morphometry were conducted on postpartum days 10 and 22. This research revealed a sexually dimorphic response, with some brain regions being larger in perchlorate-treated male rats than in comparable controls. Even so, there was no evidence of any obvious exposure-related effects on male rat brain weights or neuropathology. The most consistent exposure-related effect in the male pups was on the thickness of the corpus callosum, with both the right- and left-sided measures of the thickness of this white matter tract being significantly greater for the male pups in the 0.1 and 1.0 mg/kg-day exposure groups. The behavioral testing suggests prenatal exposure to ammonium perchlorate does not affect the development of gross motor movements in the pups.

Developmental Exposure to Perchlorate Alters Synaptic Transmission in Hippocampus of the Adult Rat

“…These findings indicate that neurologic impairment is associated with modest degrees of thyroid hormone insufficiency and support previous animal studies of neurodevelopmental sequelae associated with low levels of perchlorate exposure (U.S. EPA 2002; York et al 2005a). …”

“…We are unaware of any nonthyroidal actions of perchlorate that could readily account for the present findings on hippocampal physiology. Previous published reports of the effects of perchlorate on neurodevelopment are limited to those of York et al (2004, 2005a, 2005b), who summarized the results of findings from regulatory guideline studies. There was some degree of overlap in dose levels used in these studies and the present report (30 mg/kg/day, ~ 300 ppm; Table 1) and considerable overlap in serum thyroid hormone reductions.…”

“…This action is sufficient to reduce circulating levels of thyroid hormone and may induce neurotoxicity in developing organisms (U.S. EPA 2002; York et al 2005a). Dohan et al (2007) recently demonstrated that the NIS transports perchlorate with a higher affinity than it does iodine, and perchlorate accumulates in breast milk.…”

Windows of sensitivity to toxic chemicals in the motor effects development

“…(For interpretation of the references to color in this figure caption, the reader is referred to the web version of this article.). Ali et al, 1986; Barański, 1984, 1985; Barański et al, 1983; Bell et al, 2007a, 2007b; Carratu et al, 2000a; Carratu et al, 2000b; Chapin et al, 1997; Colomina et al, 2005; Dorman et al, 2000; Faber et al, 2007; Fechter and Annau, 1980; Garey et al, 2005; Giustino et al, 1999; Goldey and Crofton, 1998; Gupta et al, 1985; Hass et al, 1995; Henck et al, 1994; Houpert et al, 2007; Kawashima et al, 1983; Manfroi et al, 2004; Mattie et al, 2000; Overmann et al, 1987; Price et al, 1986; Rodrigues et al, 1993; Roig et al, 2006; Singh, 1986; Spyker and Avery, 1977; Squibb and Tilson, 1982; Szász et al, 1999; Taylor et al, 2002; York et al, 2005; Zaidi et al, 1984; Zaman et al, 1993.…”

Perchlorate Toxicity and Risk Assessment

“…Several studies of perchlorate in rodents have been conducted in which hormone measurements and thyroid histopathology have been evaluated. Data are available in male and female rats following 14 and 90 days of e~~o s u r e , '~"~ female mice following 90 days of e~~o s u r e , '~"~ rat dams on 9,19,20 gestation day 20, post natal day 5, postnatal day 10, and male and female pups on post natal days 5, 10, and 22. 9~19,20 A 90-day subchronic bioassay determined that the thyroid was the only target organ in male and female rats exposed to perchlorate in drinking water (0, 0.01, 0.05, 0.2, 1.0, and 10 mglkg-day) for 90 days.…”